Hepatitis C subtype distribution in chronically infected patients with mild liver fibrosis in France: the GEMHEP study.

Treatment options for Hepatitis C infection have greatly improved with direct-acting antiviral (DAA) combinations achieving high cure rates. Nevertheless, the cost of this treatment is still high and access to treatment in many countries has been preferentially reserved for patients with more severe fibrosis (F3 and F4). In this French nationwide study, we investigated the epidemiological characteristics and genotype distribution of hepatitis C virus (HCV) in treatment-naive patients with METAVIR fibrosis stages between F0 and F2 in order to identify patient profiles that became eligible for unrestricted treatment in a second period. Between 2015 and 2016 we collected data from nine French university hospitals on a total of 584 HCV positive patients with absent, mild or moderate liver fibrosis. The most represented genotypes were genotype 1b (159/584; 27.2%), followed by genotype 1a (150/584; 25.7%); genotype 3 (87/584: 14.9%); genotype 4 (80/584; 13.7%). Among genotype 4: 4a was predominantly encountered with 22 patients (27.5% of genotype 4). Genotypes 1b and 1a are currently the most frequent virus types present in treatment-naive patients with mild fibrosis in France. They can be readily cured using the available DAA. Nevertheless, non-a/non-d genotype 4 is also frequent in this population and clinical data on the efficacy of DAA on these subtypes is missing. The GEMHEP is the French group for study and evaluation of viral hepatitis on a national scale. Data collection on epidemiological and molecular aspects of viral hepatitis is performed on a regular basis in all main French teaching hospitals and serves as a basis for surveillance of these infections. Analysis and trends are regularly published on behalf of the GEMHEP group. Data collection was performed retrospectively over the 2015-2016 period, covering nine main university hospitals in France. A total of 584 hepatitis C positive patients were included in this study. Genotyping of the circulating viruses showed a high prevalence of genotypes 1b and 1a in our population. The epidemiology of hepatitis C is slowly changing in France, particularly as a consequence of the rise of 'non-a non-d' genotype 4 viruses mainly originating from African populations. More data concerning treatment efficacy of these genotypes is needed in order to guide clinical care.

Human papillomavirus does not play a role in the Barrett esophagus: a French cohort.

The role of human papillomavirus (HPV) in Barrett's esophagus (BE) has been examined but remains unclear. The purpose of the study is to dispute the connection between HPV and BE in a prospective case-control study. Biopsies were performed above and inside the Barrett's segment for BE patients and in the distal third of the esophagus for control patients for histological interpretation and for virological analysis. Biopsies for virological analysis were placed in a virus transport medium and immediately frozen in liquid nitrogen. Virological analysis involved real-time PCR using the SyBr® green protocol with modified SPF10 general primers. A total of 180 patients (119 control and 61 BE, respectively) were included. In BE patients, 31, 18, and 12 patients had, respectively, no dysplasia, low-grade dysplasia, and high grade dysplasia. Overall, nine were found to be HPV positive: five were control patients and four BE patients. HPV positive status was not associated with BE. No factors were associated with HPV, in particular the degree of BE dysplasia. HPV infection appears unlikely to be significant in the etiology of BE compared with control patients. (ClinicalTrials.gov, Number NCT02549053).

A phase II study on the efficacy and safety of procedural analgesia with fentanyl buccal tablet in cancer patients for the placement of indwelling central venous access systems.

BACKGROUND: Pain in cancer patients is often related to oncologic therapies and diagnostic procedures. The placement of fully implantable venous access systems is a very common procedure in oncology patients. Local anaesthesia is the method most commonly used to overcome pain related to this surgical procedure, but the local anaesthetic may be unable to completely eradicate all pain. This study investigates the effectiveness and safety of fentanyl buccal tablet (FBT), administered by OraVescent® technology, in reducing procedural pain related to the placement of indwelling central venous access systems (Ports) in opioid-naïve cancer patients. METHODS: Inpatients who required an indwelling vascular access (Port) were preoperatively assessed with a self-assessment questionnaire on anxiety and pain. A 100 µg FBT was administered 10 min before preparation of the operating field. A self-assessment scale for pain experienced during the procedure was administered at the end of the procedure. Vital signs and the presence of any side effects or bothersome symptoms were monitored during the procedure, at the end, and 4 h later. RESULTS: From October 2012 to June 2014, 65 patients were enrolled in the study. A total of 61 (93.9 %) patients perceived no or a little pain during the procedure. Four patients (6.2 %) reported a lot of pain. No patient reported very severe pain. This data is significant in terms of the lower than expected presence of pain (Fisher test p = 0.0018) as assessed in our previous experience without procedural analgesia. The most common side effects of FBT was drowsiness, experienced by 28 patients at the end of the procedure (43.1 %), significantly reduced (p < 0.01) to 8 patients after 4 h (12.5 %). Nausea was present in 6 cases at the end of the procedure (9.2 %) and in 7 cases 4 h later (10.9 %). Vomiting was present in 3 cases at the end (4.7 %) and in 2 other patients after 4 h (7.8 %). No significant change of vital parameters was observed between the baseline and the subsequent measurements in all patients studied. CONCLUSIONS: The significant improvement in the number of patients experiencing little or no pain, accompanied by a lower number of non-severe side effects, suggests that FBT is a valid, practical and safe method of procedural analgesia. It will be necessary to perform further studies, taking into account the need for standard antiemetic pre-medication to minimise the incidence of nausea and vomiting.

Correlation between the promoter basal core and precore mutations and HBsAg quantification in French blood donors infected with hepatitis B virus.

Hepatitis B virus (HBV) basal core promoter (BCP) and precore (PC) mutations, HBV viral load and HBV surface antigen (HBsAg) quantitation were screened to assess correlations between these HBV markers in asymptomatic chronic hepatitis B carriers in France. From January 2006 to July 2007, 200 sera were collected from patients who were discovered to be HBsAg-positive when they volunteered to give blood. Direct sequencing of precore/core gene was used to detect A1762T/G1764A mutations in the BCP and G1896A in the PC region. HBV viral load and HBsAg were quantified with two commercials assays. The prevalence of the BCP and PC mixed/mutants were 37% and 60% respectively (P = 0.0001). HBV DNA level and HBsAg titer were significantly lower in subjects harboring the mixed/mutant PC virus compared to those infected by the wild phenotype. No significant difference was observed in HBV viral loads of blood donors infected by wild or mixed/mutant BCP viruses. Mutant or mixed PC virus was associated with male gender, HBeAb-positive status and HBV/D and HBV/E genotypes. BCP mutations were associated with age, and both HBV/A-HBV/E genotypes.The genetic properties of HBV in this cohort showed that most of the blood donors had a negative HBeAg serological status and harbored the PC mutant phenotype in combination with low levels of both HBV DNA and HBsAg. As the study was conducted in healthy subjects who could be considered as asmptomatic carriers, these results suggest a possible protective effect of the G1896A mutation against severe liver lesions.

[Results of a novel real-time PCR, sequence analysis, Inno-LiPA line probe assays in the detection of hepatitis B virus G1896A precore mutation in French blood donors]. / Résultats de trois méthodes pour la détection de la mutation précore G1896A du virus de l'hépatite B chez les donneurs de sang français : PCR temps réel, séquençage et test Inno-LIPA.

AIM: To screen hepatitis B virus (HBV) genotypes and associated basal core promoter (BCP; T1762A/A1764) and precore (PC; A1896) mutations among the 100 HBV surface antigen (HBsAg) positive voluntary blood donors in France. METHODS: HBV genotypes were determined by using direct sequence analysis. Three methods were used to detect G1896A mutation: non-commercial real-time PCR (PCRTR°, line probe assay (InnoLiPA HBV PreCore, INNOGENETICS(®)) and direct sequencing of precore gene. HBV viral load was quantified with two commercial real-time PCR (COBAS(®) AmpliPrep/COBAS(®) TaqMan(®) HBV Test/Roche and Real Time HBV/M2000/Abbott). RESULTS: The mean age of donors was 30 (18-64). Patients were from Africa (42%), Europa (50%), and Asia (8%). HBV/D was the most predominant (37%) genotype followed by HBV/A (31%) and HBV/E (22%). PC and BCP mutants were found in 57% with Inno-LIPA HBV test and 59% with both PCRTR and sequencing methods. A significant difference in the viral load of blood donors with wild and PC mutants was observed with the Taqman Cobas real time PCR (3,19 Log(10) UI/ml versus 4,93 Log(10) UI/ml, p < 0.05). Precore phenotype determination was in agreement with the three PC mutation detection methods in 56% of cases. CONCLUSIONS: Non-Caucasian genotype E was present in the French blood donors. PC mutation was more common than BCP mutations in this study. As HBV infected blood donors were more often asymptomatic carriers, we could speculate that the G1896A mutation may favour the asymptomatic state, supporting previous observations.

Early and short-term acenocumarine or dalteparin for the prevention of central vein catheter-related thrombosis in cancer patients: a randomized controlled study based on serial venographies.

BACKGROUND: We evaluated efficacy and safety of early and short-term prophylaxis with acenocumarine or dalteparin in the prevention of non-occlusive or occlusive central vein catheter-related thrombosis (CVCrT). PATIENTS AND METHODS: Consecutive cancer patients scheduled for chemotherapy randomly received: acenocumarine 1 mg/day for 3 days before and 8 days after central vein catheter (CVC) insertion; dalteparin 5000 IU 2 h before and daily for 8 days after CVC insertion; no anticoagulant treatment (NT). All patients underwent venography on days 8 and 30, some of them on days 90, 150 and 210 after CVC. RESULTS: A total of 450 patients were randomized, 348 underwent at least two venography. Both acenocumarine and dalteparin reduced venography-detected CVCrT rate [21.9% acenocumarine versus 52.6% NT, odds ratio (OR) 0.3, P < 0.01; 40% dalteparin versus 52.6% NT, OR 0.6, P = 0.05]. Acenocumarine was more effective than dalteparin (OR 0.4, P = 0.01). The rate of occlusive CVCrT was not different in the three groups (0.9% acenocumarine, 3.3% dalteparin, 1.8% NT; P = 0.40). Most CVCrTs (95.6%) were observed on day 8 after CVC insertion and were non-occlusive. CONCLUSIONS: In this study of early and short-term prophylaxis, acenocumarine was more effective than dalteparin on non-occlusive and asymptomatic CVCrT events. The first days following CVC insertion represent the highest risk for CVCrT.

Genetic diversity of the hepatitis C virus: impact and issues in the antiviral therapy.

The hepatitis C Virus (HCV) presents a high degree of genetic variability which is explained by the combination of a lack of proof reading by the RNA dependant RNA polymerase and a high level of viral replication. The resulting genetic polymorphism defines a classification in clades, genotypes, subtypes, isolates and quasispecies. This diversity is known to reflect the range of responses to Interferon therapy. The genotype is one of the predictive parameters currently used to define the antiviral treatment strategy and the chance of therapeutic success. Studies have also reported the potential impact of the viral genetic polymorphism in the outcome of antiviral therapy in patients infected by the same HCV genotype. Both structural and non structural genomic regions of HCV have been suggested to be involved in the Interferon pathway and the resistance to antiviral therapy. In this review, we first detail the viral basis of HCV diversity. Then, the HCV genetic regions that may be implicated in resistance to therapy are described, with a focus on the structural region encoded by the E2 gene and the non-structural genes NS3, NS5A and NS5B. Both mechanisms of the Interferon resistance and of the new antiviral drugs are described in this review.

[An experience of hepatitis B control in a rural area in Far North Cameroon]. / Une expérience de lutte contre l'hépatite B en zone rurale à l'extrême nord du Cameroun.

Experience of four years of control of the transmission of hepatitis B in a rural area in Far North Cameroon is presented: (i) prevention of mother to child transmission, (ii) HBsAg screening before blood transfusion, (iii) detection of HIV/HBV co-infections, (iv) protection of healthcare workers. The prevalence of HBsAg is very high in the four populations studied: 18.2% of pregnant women, 16.9% of candidate for blood donation, 14.4% of people living with HIV and 18 % of healthcare workers. Despite limited resources, effective actions are possible. Prevention of mother to child transmission of HBV with vaccination at birth has been set up, with bottlenecks - similar to those observed in HIV - but decreasing over the study. The screening of all potential blood donors has been reached over the years for HIV, HBsAg and HCV, which has led to the eviction of one out of five potential blood donors. Screening of healthcare workers reminded us that adult protection is based on a very early vaccination and not when hiring, even if it is possible to diagnose rare adults eligible for vaccination by research of anti-HBc antibody. A program of hepatitis B control, essential in Africa, appears feasible in rural areas in a framework of an overall improvement in care delivery.

Identification of a duplicated V3 domain in NS5A associated with cirrhosis and hepatocellular carcinoma in HCV-1b patients.

BACKGROUND: The NS5A protein of the hepatitis C virus has been shown to be involved in the development of hepatocellular carcinoma. OBJECTIVES: In a French multicenter study, we investigated the clinical and epidemiological features of a new HCV genotype 1b strain bearing a wide insertion into the V3 domain. STUDY DESIGN: We studied NS5A gene sequences in 821 French patients infected with genotype 1b HCV. RESULTS: We identified an uncharacterized V3 insertion without ORF disruption in 3.05% of the HCV sequences. The insertion comprised 31 amino-acids for the majority of patients; 3 patients had 27 amino-acids insertions and 1 had a 12 amino-acids insertion. Sequence identity between the 31 amino-acids insertions and the V3 domain ranged from 48 to 96% with E-values above 4e(-5), thus illustrating sequence homology and a partial gene duplication event that to our knowledge has never been reported in HCV. Moreover we showed the presence of the duplication at the time of infection and its persistence at least during 12 years in the entire quasispecies. No association was found with extrahepatic diseases. Conversely, patients with cirrhosis were two times more likely to have HCV with this genetic characteristic (p=0.04). Moreover, its prevalence increased with liver disease severity (from 3.0% in patients without cirrhosis to 9.4% in patients with both cirrhosis and HCC, p for trend=0.045). CONCLUSIONS: We identified a duplicated V3 domain in the HCV-1b NS5A protein for the first time. The duplication may be associated with unfavorable evolution of liver disease including a possible involvement in liver carcinogenesis.

A multicenter double-blind study comparing lovastatin and gemfibrozil in the treatment of primary hypercholesterolemia.

The efficacy and tolerability of lovastatin and gemfibrozil were compared in a randomized double-blind 12-week study including 182 patients with primary hypercholesterolemia, from 7 hospitals in Spain. Inclusion criteria were total-cholesterol of at least 250 mg/dl and triglycerides less than 350 mg/dl. Patients were stratified in two groups: group 1, cholesterol less than 300 mg/dl, and group II, cholesterol equal to or more than 300 mg/dl. Patients were randomized to gemfibrozil (600 mg b.i.d.) or lovastatin (20 mg q.p.m., group I and 40 mg q.p.m., group II). If after 6 weeks of treatment cholesterol remained above 200 mg/dl, lovastatin does were doubled. In group I, lovastatin decreased cholesterol by 20%, LDL-C by 28%, and triglycerides by 17%, and increased HDL-C by 8%. In group II the results were: -26%, -33%, -19% and +6% respectively. The corresponding results with gemfibrozil were: -8%, -9%, -28% and +14% (group I); and -13%, -14%, -33% and +9% (group II). In both groups, lovastatin was more effective in reducing cholesterol and LDL-C (P less than 0.001) and gemfibrozil in reducing triglycerides (P less than 0.05 group I and P less than 0.01 group II). Both drugs were well tolerated. Thus, lovastatin and gemfibrozil are effective lipid-lowering agents; lovastatin has more pronounced effects in patients with hypercholesterolemia.

Mixed cryoglobulinemia and hepatitis C virus.

BACKGROUND: Mixed cryoglobulinemia (MC) is frequently associated with clinical and biological evidence of liver disease and has recently been reported in cases of hepatitis C virus (HCV) infection. The aim of this study was to assess prospectively in a large series of MC patients: (1) the prevalence of HCV markers (anti-HCV antibodies and HCV RNA in serum and cryoprecipitate); (2) the main clinical, biologic and liver histologic features in patients with or without HCV infection. PATIENTS: One hundred fifteen consecutive unselected MC patients were studied: 45% had well-defined underlying diseases ("nonessential" MC). Fifty-five percent with no cause of MC were considered to have "essential" MC and were subjected to in-depth examination. METHODS: Patients were considered to have MC if two successive determinations of their serum cryoglobulin level were above 0.05 g/L. Anti-HCV antibodies (Ab) were detected in all patients by second-generation tests (ELISA, RIBA). We also looked for HCV RNA sequences amplified by polymerase chain reaction (PCR) in the sera and cryoprecipitates of 39 patients; HBs antigen, anti-HBs Ab and anti-HBc Ab in all patients; and HBV DNA in 20 sera and 17 cryoprecipitates. Quantitative HCV Ab and RNA studies were performed on whole serum, cryoprecipitates, and supernatants. Clinical features were recorded retrospectively for each patient. Liver biopsies from 23 anti-HCV Ab-positive and 7 anti-HCV Ab-negative patients were examined histologically, with qualitative and quantitative analysis. RESULTS: Anti-HCV Ab were found in 47/115 (41%) patients by ELISA and RIBA: 33/63 (52%) essential MC and 14/52 (27%) nonessential MC. Among the 63 essential MC patients, the 33 anti-HCV Ab-positive (Group 1) were compared to the 30 anti-HCV Ab-negative patients (Group 2). Group 1 patients had more cutaneous involvement (Raynaud's phenomenon, purpura, livedo, distal ulcers, or gangrenous changes) (17 versus 5: p = 0.004), higher alanine aminotransferase levels (110 +/- 22 versus 41 +/- 10 IU; p < 0.005), higher serum cryoglobulin levels (0.35 +/- 0.07 versus 0.12 +/- 0.04 g/L; p = 0.01), lower CH50 (28 +/- 3 versus 44 +/- 2 CH50/mL; p = 0.0001) and lower C4 levels (0.20 +/- 0.02 versus 0.29 +/- 0.03 g/L; p < 0.04). The prevalence of HBV serum markers was low in both groups, and HBV DNA was never detected in any of the sera and cryoprecipitates tested. HCV RNA sequences were detected in 10/16 (63%) sera and 12/16 (75%) cryoprecipitates from Group 1 patients, whereas they were not in the sera or cryoprecipitates from 23 Group 2 patients. Using quantitative PCR, HCV RNA in cryoprecipitates was concentrated 20 to 100 times despite the absence of significant anti-HCV Ab concentration in these samples. Histologic examination of liver biopsies revealed a spectrum of lesions ranging from chronic active hepatitis to cirrhosis, but Knodell's score did not differ between the groups. CONCLUSION: (1) About 50% of the essential MC patients had anti-HCV Ab, and these patients had more severe cryoglobulinemia-associated clinical and biological signs; (2) HCV RNA sequences were found in the large majority of sera and cryoprecipitates from patients with essential MC and anti-HCV Ab and were more concentrated in cryoprecipitates than in supernatants. These results suggest a role for HCV in the pathogenesis of MC and indicate that many cases of essential MC may be secondary to HCV infection and thus nonessential.

Characterization of hyperlipidemia in two patients with analbuminemia.

The results of plasma lipid and lipoprotein analysis in two related patients, brother (R.U.) and sister (R.R.) with analbuminemia, and three first-degree relatives (parents and sister) are reported. Both patients showed a remarkable increase in cholesterol and phospholipid levels, and there was a corresponding increase in serum apo B and apo A-I. This hyperlipidemia is due to a selective increase in LDL and HDL concentrations. R.U. showed an increase in both HDL2- and HDL3-cholesterol, R.R. only in HDL3-cholesterol. VLDL concentration was reduced in R.U. and normal in R.R. The plasma lipoprotein electrophoretic pattern did not correspond to any of the phenotypes in Fredrickson's classification. Composition of the different lipoprotein fractions was normal in the patients and family members. Serum FFA level in R.R. was very low. An increase in the plasma protein fractions, particularly the transport fractions, was confirmed in both patients. The possible pathophysiology of the hypercholesterolemia in these patients is discussed. Unlike other reported cases, clinical signs of atherosclerotic complications were absent.

Randomized trial of 5-fluorouracil and high-dose folinic acid with or without alpha-2B interferon in advanced colorectal cancer.

We evaluated the role of low-dose alpha-2b interferon, added to chemotherapy, for advanced colorectal cancer; we randomized patients, to either a combination chemotherapy of 5-fluorouracil (5-FU) and high-dose folinic acid (HDFA) or the same regimen plus interferon. Between January 1990 and March 1992, 100 untreated patients (PTS) with advanced colorectal cancer, 53 men and 47 women, with an ECOG performance status (PS) of < or = 3, were randomized to either HDFA 200 mg/m2 iv bolus and 5FU 370 mg/m2 in 15-min iv infusion days 1-5 every 4 weeks (arm A), or the same chemotherapy plus IFN 3 x 10(6) IU subcutaneously three times a week in chemotherapy intervals (arm B). A total of 97 PTS are evaluable for response, toxicity, and survival; 3 PTS are not evaluable in arm B for major protocol violations. PTS characteristics were well balanced in both arms for age (median, 64 years), disease-free survival, and disease site. ECOG PS was 0 in 28% of PTS in arm A and in 13% in arm B. Response rates were as follows: arm A, 40%; and arm B, 23%. Median time to failure was as follows: 10.2 months arm A versus 9 months arm B. Median survival was as follows: 13.3 months arm A versus 10.9 months arm B. Grade 3 haematological toxicity was 9% of PTS in both arms. Gastrointestinal toxicity was as follows: 17% arm A versus 22% arm B. The cost of drugs expressed per m2/month was $60 in arm A and $390 in arm B. The results show that IFN at the schedule and doses employed adds no benefit to the combination of 5FU/HDFA.

Pulmonary involvement in tuberous sclerosis complex: presentation of a case.

A clinical case of a pulmonary involvement in Tuberous Sclerosis Complex is reported. This rare involvement (1%) is characterized by either interstitial disease or bullae; therefore, pneumothorax is likely to happen in lung parenchyma. Furthermore this complication induces a progressive serious respiratory failure until the death of the patient.

Clinical diagnostic application of 111In-DTPA-octreotide scintigraphy in small cell lung cancer.

Some years ago it was proved that a good percentage of small cell lung cancers, classified among cancers of the APUD system, produces somatostatin receptors that can be detected in vivo by scintigraphy with 111In-DTPA-octreotide. With the method in the whole body it is possible to identify the principal neoformation and the probable metastases. The authors present a study of 21 patients afflicted with small cell lung cancer diagnosed histologically. The study, carried out between January 1995 and December 1997, compared the radiologic iconography of the CT scan with the scintigraphic map obtained by a planar scintigraphy and in SPECT 1, 4 and 24-hr after iv injection of 110 MBq of 111In-DTPA-octreotide. The comparison was made with reference to the principal neoplasm and probable metastases. A scintigraphic study, a CT of restaging and a follow-up, done after 3 and 6 months of chemotherapy, on 15 patients with cancer that produces somatostatin receptors proved that the neoplasm sometimes regresses and sometimes progresses. In the latter case, it is possible to identify cerebral, mediastinal and hepatic metastases with the administration of 200 microg of octreotide 3 times a day for 7 days before the scintigraphy. In fact, the administration lowers background activity. The authors concluded that scintigraphy with 111In-DTPA-octreotide plays an important part in the study of patients afflicted with small cell lung cancer. Scintigraphy identifies the subgroups of patients who can be cured with somatostatin analogues together with chemotherapy. Scintigraphy presents a good sensibility in the re-staging and in the follow-up of patients who are treated, even though it is difficult to identify subdiaphragmatic metastases where liver, spleen and kidney show an increase in 111In-DTPA-octreotide.

[Screening tests of anti-HVC antibodies used in France. Analysis of sensitivity]. / Les trousses de dépistage des anticorps anti-VHC utilisées en France. Analyse de la sensibilité. Groupe de Travail "Hépatites Virales" de la Société Française de Transfusion Sanguine.

The results concerning the hepatitis C antibodies screening tests sensitivity are presented by Viral Hepatitis Study Group of the French Society of Blood Transfusion. This evaluation was carried out in 1993, with five tests available for Hepatitis C Viral (HCV) antibodies screening. Several panels of human blood samples, collected by members of Viral Hepatitis Study Group, were used. For those specimens the data about whole serology (various reactivities against viral antigens) clinical history and other explorations (molecular biology, liver histology, other viral infections) are described. If possible all those results are used to describe some interpretation criteria for the HCV serology and sensitivity obtained for each screening test.

[Interferon alpha-2a treatment of 26 patients with chronic non-A non-B hepatitis. Predictive factors of response]. / Traitement par l'interféron alpha-2a de 26 cas d'hépatites chroniques non A-non B. Etude des facteurs prédictifs de réponse.

The type and predicting factors of response to alpha interferon therapy have been studied in 26 patients with chronic non-A non-B hepatitis. Interferon was administered three times weekly during 6 months at a dose of 3 millions units/day. Eleven patients (42 percent) had serum alanine aminotransferase levels below 1.5 times the upper limit of normal range at the end of treatment. Only eight (31 percent) patients had persistent normalization of seric alanine aminotransferase value, 6 months after the end of the interferon treatment. The main factors involved in the response to therapy were age, apparent duration of the disease, and mode of contamination: patients who responded to interferon were younger, had a shorter duration of hepatitis and a parenterally transmitted disease.

[Hemorheologic changes in patients with obliterative arteriopathy of the leg before and after muscle exercise tests]. / Modifications hémorhéologiques chez les sujets atteints d'artériopathie oblitérante des membres inférieurs avant et aprés un test d'effort musculaire.

Blood and plasma viscosity, erythrocyte filtrability and blood gas analysis were determined in 25 subjects with arteriosclerosis obliterans of the lower limbs before and after a muscle exercise test. Thirty-six shear rates between 0 and 230 s1 were studied to obtain viscosity curves, and regression analysis was performed for each curve. Mean viscosity curves for pathologic and control populations were plotted. The purpose of the study was to determine whether viscosity curves for blood and plasma before and after exercise, based on a high number of measurements, can provide information on rheological changes during intermittent claudication. Practically all viscosity curves in pathologic and control subjects could be described using a hyperbolic equation. Plasma as well as blood viscosity increased in pathologic subjects after exercise. However, erythrocyte filtrability and blood gas analysis in pathologic and control subjects, and blood and plasma viscosity in control subjects, showed no statistically significant changes after exercise. It is suggested that muscle exercise in reduced blood flow conditions can alter the aggregation of macromolecular complexes of plasma proteins, which could have an influence on cell components by modifying blood rheological behavior during claudication.

[Exposure of distal internal carotid artery through mandibular vertical ramus osteotomy]. / Accesso chirurgico all'arteria carotide interna distale medicante osteotomia mandiobolare verticale.

Exposure of the distal internal carotid artery at the level of the second cervical vertebra required manoeuvers such as division of digastric muscle or mandibular subluxation. These increase the exposure but may not provide adequate access and are associated with significant cranial nerves or temporal mandibular joint complications. Vertical Ramus Osteotomy (VRO) provided access of the internal carotid artery (ICA) up to the base of the skull, with low incidence of cranial nerve injury temporo-mandibular joint (TMJ) pain and no preincision preparation. We report two cases in which vertical division of the mandibular ramus provided access of the ICA up to the base of the skull. Preoperative Duplex Scan examination and in the second case the arteriography revealed ICA preocclusive stenosis within 1.5 cm of the skull base. VRO was performed trouhgh a standard neck incision and miniature titanium plates were used to reapproximate the mandible after vascular procedure. There were no death, cranial nerve injury, mandibular nonunion, malocclusion or TMJ pain. We found that VRO is useful when carotid artery pathology extends beyond the usual field of exposure, avoiding nerve injury or TMJ lesion and requires no additional pre-incision preparation.

Primary pulmonary hypertension in a HIV+ patient.

Recent reports have suggested a possible association between HIV infection and primary pulmonary hypertension (PPH). We report the case of a HIV+ patient, without manifestations of the acquired immune deficiency syndrome (AIDS), who presented with signs of elevated pulmonary arterial pressure.